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Docetaxel down‐regulates the expression of androgen receptor and prostate‐specific antigen but not prostate‐specific membrane antigen in prostate cancer cell lines: Implications for PSA surrogacy
Author(s) -
Kuroda Kenji,
Liu He,
Kim Sae,
Guo Ming,
Navarro Vincent,
Bander Neil H.
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21004
Subject(s) - lncap , prostate cancer , androgen receptor , docetaxel , cancer research , prostate specific antigen , glutamate carboxypeptidase ii , prostate , androgen , bicalutamide , antigen , flow cytometry , cell culture , medicine , endocrinology , cancer , biology , immunology , hormone , genetics
BACKGROUND Docetaxel (DOC) has potent anti‐tumor efficacy as a result of promoting microtubule assembly and microtubule bundling thereby impairing mitosis. Knowing that some anti‐microtubule agents affect the polarity of prostate‐specific membrane antigen (PSMA) expression and that androgen ablation can up‐regulate PSMA expression, we sought to determine any effect of DOC on PSMA expression in prostate cancer (PC) cell lines as a prelude to a clinical effort. As controls, we also looked at the expression of androgen receptor (AR) and prostate‐specific antigen (PSA). METHODS The effect of DOC on cell viability and PSMA, AR, and PSA expression was examined by flow cytometry and immunoblotting using LNCaP, CWR22Rv1, and MDA‐PCa‐2b cells. The effect of DOC on PSA levels of LNCaP and MDA‐PCa‐2b cells was also measured in conditioned media. The effect of DOC was also studied using LNCaP and MDA‐PCa‐2b cells that were transfected to over‐express AR. RESULTS PSMA levels were not affected by DOC treatment. Unexpectedly, we found DOC significantly down‐regulated both AR and PSA in a dose‐dependent manner in the cell lines studied. Over‐expression of AR partially abrogated the cytotoxic effects of DOC. CONCLUSIONS While DOC did not affect PSMA expression, it was unexpectedly found to down‐regulate AR and PSA. DOC‐induced down‐regulation of AR might be one of the anti‐tumor mechanisms active in PC. Down‐regulation of PSA may account for the significantly higher PSA response rates (45–50%) relative to measurable response rates (8–17%) reported in DOC PC trials and have implications for PSA surrogacy observations derived from DOC trials. Prostate 69: 1579–1585, 2009. © 2009 Wiley‐Liss, Inc.